Theaflavin Inhibits LPS-Induced IL-6, MCP-1, and ICAM-1 Expression in Bone Marrow-Derived Macrophages Through the Blockade of NF-κB and MAPK Signaling Pathways

Abstract

Theaflavin, the main polyphenol in black tea, has anti-inflammatory, antioxidative, anti-mutagenic, and anti-carcinogenic properties. The aim of this study was to evaluate the effects of theaflavin on lipopolysaccharide (LPS)-induced innate signaling and expression of pro-inflammatory mediators in bone marrow-derived macrophages isolated from ICR mice. The effects of theaflavin on the expression of proinflammatory mediators, LPS-induced nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways were examined by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. LPS-induced interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) expression was inhibited by theaflavin. LPS-induced inhibitor kappa B alpha (IκBα) degradation and nuclear translocation of RelA were blocked by theaflavin. LPS-induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK), and p38 MAPK was inhibited by theaflavin. The inhibitory effect of theaflavin on IL-6, MCP-1, and ICAM-1 expression was completely inhibited by Bay11-7082 (NF-κB inhibitor). The inhibitory effect of theaflavin on IL-6 and ICAM-1 expression was inhibited by SB203580 (p38 MAPK inhibitor). The inhibitory effect of theaflavin on MCP-1 expression was inhibited by SP600125 (JNK inhibitor). These results indicate that theaflavin prevents LPS-induced IL-6, MCP-1, and ICAM-1 expression through blockade of NF-κB and MAPK signaling pathways in bone marrow-derived macrophages.